The primary goal of this research project is to further our understanding of the mechanisms by which brain peptides regulate the hormonal secretions of the pituitary gland during sexual maturation. Although numerous recent reports including our own (Blank et al. 1979, 1980) have implicated endogenous morphine-like substances in the tonic secretion of several pituitary hormones, they have not elucidated the mode-of-action of these endogenous substances. Using exogenous opiate peptides (opioids) or opiate antagonists it will be our goal to clarify the extent of brain peptide involvement in pituitary function. We will examine luteinizing hormone (LH) and prolactin (PRL) secretion in vivo and in vitro in immature female rats. This model is chosen because our data suggest that endogenous opioids participate in the control of LH (and possibly PRL) secretion during pubertal development. Developing rats show the greatest release of LH in response to opiate receptor blockade with naloxone during two discrete periods before puberty. The latter age period (22-26 days) which ends at least 10 days before the onset of puberty is a 'critical period' for several endocrine maturational events. We will focus on this age period to determine the site-of-action, extent of interplay with neurotransmitters and effects on pubertal timing of endogenous opioids. To accomplish these goals, we will: determine the serum LH response to opioids or their antagonists injected either centrally or peripherally; critically examine the effects on LH and PRL of centrally administered opiate antagonists that are hydrophilic (quaternary naloxone and naltrexone) or ultra-long-acting (chlornaltrexamine); determine the LH response to opioids or opiate antagonists in the presence of monoamine receptor blockers; measure the in vitro release of LH from immature rat pituitaries incubated with opioids, protease inhibitors and LHRH; and determine, by three independent criteria, the effects on sexual maturation of long and ultra-long-acting opiate antagonists. This project will not only enhance our knowledge of the physiological processes which govern pubescence but also will have potential importance in developing therapies for human disorders such as precocious puberty, galactorrhea, amenorrhea and fertility problems related to neuroendocrine dysfunction.